Worldwide, it is estimated that 4.3 million people die of cancer each year and that roughly 70 percent of the terminally ill cancer patients experience pain as a major symptom during the course of their disease. Even though the majority of these patients receive opioids for pain management, up to 30 percent still experience breakthrough pain that is considered moderate to severe. The goal of this proposal is to develop a noninvasive, cost effective alternative to treat incident pain in cancer patients. This proposal describes an oral transmucosal (OT) drug delivery formulation for the noninvasive administration of high potency opioids (fentanyl, sufentanil, and alfentani) using a unique, titratable, dose-to-effect formulation. The OT delivery approach is designed for patient controlled pain management and is easily used in a hospital setting or for outpatient pain management therapy. Phase I work will optimize the OT delivery formulation for fentanyl, sufentanil, and alfentanil. Formulation variables include three matrices and three buffer conditions. Dissolution kinetics will be determined for each proposed formulation. A dog model has been developed to screen potential formulations using a buccal cell designed to evaluate drug depletion kinetics. The dog drug depletion model will be validated by determining plasma drug levels over time using a radioimmunoassay technique. Preliminary animal experiments indicate that the buccal transmucosal permeability coefficient of fentanyl can vary depending on the base material and can significantly improve the bioavailability of fentanyl and should have a similar effect on sufentanil and alfentanil.